Interferons are a family of proteins or glycoproteins produced by cells in response to viral infections or other inducing agents, such as double-stranded RNA or mitogens. Interferons are released from the producing cells and interact with other cells to confer on them a broad antiviral resistance. In addition, they inhibit cell proliferation and modulate the immune response (Stewart W. E., 1979, The Interferon System, Springer).
Interferons, produced by different cells, were found to differ in their physicochemical, serological and functional properties. Human interferons are now grouped into three categories--.alpha., .beta., and .gamma., based on their antigenic specificities; a similar classification can be applied to murine interferons.
In order to limit economical losses provoked by viral diseases of cattle, the availability of an antiviral agent of a wide spectrum of action is of importance. High morbidity is observed under certain circumstances, such as transport of animals or their regroupment in a new environment, where they are confronted with new viral infections. Prophylactic or therapeutic use of bovine interferons seem to be ideal in these circumstances.
The bovine interferons (BoIFN), unlike their counterparts from human or murine sources, have not been extensively studied. BoIFN are likely to be a potent agent for the prevention of virus mediated cattle diseases such as Foot and Mouth Disease, Infectious Bovine Rhinotracheitis, Pseudorabies, Bluetongue and Neonatal Bovine Diarrhea. When BoIFN preparations were tested in vitro, they exerted antiviral activity against some of the viruses involved in these diseases (Goossens, A et al Ann. Met. Vet. 127 p. 135 1983).
.alpha.-Interferons are a family of related proteins coded by over a dozen distinct genes. This was demonstrated in mice, humans and now as shown by us also in cattle. (Goeddel D. U. et al 1981 Nature 290 20; Nagata S et al 1980, Nature 287,401; Shaw et al 1983, Nuc. Acid. Res. 11 555; Wilson et al 1983 J. Mol. Biol. 166, 457). The IFN.alpha. genes have substantial sequence homology, yet they are conserved throughout the evolution. It is therefore believed that differential in vivo production of appropriate interferons is required for a successful defensive response in humans to specific viral infections, immunological interferences and neoplastic disorders.
The major obstacle for a clinical evaluation of predetermined combination of .alpha.-interferon preparations stems from the difficulties in obtaining large quantities of the purified proteins of each one of the interferon types. The techniques of genetic engineering provided the tools for obtaining a reliable source for the production of individual IFN.alpha. proteins. These techniques allow one to isolate the genetic information of each interferon, by direct manipulation of the genome or its transcription products, or by chemical synthesis of the complete IFN.alpha. coding sequence, and to clone this information in prokaryotic or eukaryotic cells. Further manipulations of these individual IFN sequences together with appropriate expression signals (transcription and translation signals) lead to high levels of production of the cloned interferons.